Anti-tubwrcular treatment for Pulmonary and extra-Pulmonary TB as per national tubercular elimination program with new updates and peer reviewed guidelines. Also mentioned what are the first line, 2nd Line, duration of treatment. What is the indication and contraindications and when to use modify ATT
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"tuberculosis"[MeSH Terms] AND "drug therapy"[MeSH Terms] AND "guidelines"
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India NTEP national tuberculosis elimination program ATT treatment guidelines 2024 2025 updated
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PMID: 40693952
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NTEP India 2024 ATT regimen pulmonary extrapulmonary TB treatment category 1 2 H R Z E bedaquiline
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Anti-Tubercular Treatment (ATT): National TB Elimination Programme (NTEP) - India
Comprehensive Clinical Guide with 2024-2025 Updates
1. OVERVIEW & NTEP FRAMEWORK
India's National TB Elimination Programme (NTEP) - rebranded from RNTCP in 2020 - operates under the National Strategic Plan (NSP) 2020-25 with four pillars: Detect - Treat - Prevent - Build, targeting TB elimination by 2025 (ahead of the SDG target of 2030).
Key 2024-2025 NTEP updates include:
- Universal Drug Susceptibility Testing (UDST) at diagnosis via CBNAAT (Xpert MTB/RIF) and Truenat
- Introduction of BPaLM regimen for DR-TB (rolled out 2024)
- Nikshay Poshan Yojana cash support doubled to INR 1,000/month (2024)
- BCG re-vaccination trial in 40 districts (September 2024)
- New CBNAAT M.tb/XDR test for rapid detection of resistance to H, FQ, SLI and Eto (August 2024)
- Guidelines for extrapulmonary TB management finalized at NTI (2024-25)
2. FIRST-LINE ATT DRUGS (Group 1)
| Drug | Abbreviation | Adult Dose | Mechanism |
|---|---|---|---|
| Isoniazid | H | 5 mg/kg/day (max 300 mg) | Inhibits mycolic acid synthesis |
| Rifampicin | R | 10 mg/kg/day (max 600 mg) | Inhibits RNA polymerase |
| Pyrazinamide | Z | 25 mg/kg/day (max 2000 mg) | Active in acidic/intracellular environment |
| Ethambutol | E | 15-20 mg/kg/day (max 1600 mg) | Inhibits arabinogalactan synthesis |
| Streptomycin | S | 15 mg/kg/day (max 1 g) | Aminoglycoside; used only in selected cases |
NTEP uses Fixed Dose Combinations (FDCs):
- Adult FDC (Intensive Phase): HRZE = 75/150/400/275 mg
- Adult FDC (Continuation Phase): HRE = 75/150/275 mg
Adult Weight Band Dosing:
| Weight | IP Tablets (HRZE) | CP Tablets (HRE) |
|---|---|---|
| 25-34 kg | 2 | 2 |
| 35-49 kg | 3 | 3 |
| 50-64 kg | 4 | 4 |
| 65-74 kg | 5 | 5 |
| ≥75 kg | 6 | 6 |
3. TREATMENT REGIMENS - PULMONARY & EXTRAPULMONARY TB
A. Drug-Sensitive TB (DS-TB) - Standard Regimen
NTEP Standard Regimen: 2HRZE / 4HRE
| Phase | Drugs | Duration | Doses |
|---|---|---|---|
| Intensive Phase (IP) | H + R + Z + E | 2 months (8 weeks) | 56 doses, daily |
| Continuation Phase (CP) | H + R + E | 4 months (16 weeks) | 112 doses, daily |
| Total | 6 months |
Note: Pyrazinamide (Z) is stopped in the continuation phase. All doses given daily under direct observation (DOT).
4-Month Novel Regimen (ATS/CDC/ERS/IDSA 2025 Update):
A new all-oral 4-month regimen (2HPMZ/2HPM: isoniazid + rifapentine + moxifloxacin + pyrazinamide) has been endorsed by the 2025 ATS/CDC/ERS/IDSA guideline (PMID 40693952) for eligible adults with drug-susceptible pulmonary TB. Children with non-severe TB may also qualify for 4-month therapy.
B. Extrapulmonary TB - Site-Specific Regimens (NTEP)
| Site | Regimen | Duration | Special Notes |
|---|---|---|---|
| Lymph node TB | 2HRZE / 4HRE | 6 months | Standard |
| Pleural TB | 2HRZE / 4HRE | 6 months | Standard |
| Pericardial TB | 2HRZE / 4HRE + steroids | 6 months | Prednisolone 1-2 mg/kg/day, tapered |
| Abdominal TB | 2HRZE / 4HRE | 6 months | Standard |
| TB Meningitis | 2HRZE / 10HRE | 12 months | CP extended to 10 months; steroids mandatory (Dexamethasone 0.4 mg/kg/day × 4 weeks, tapered) |
| Skeletal/Spinal TB (Pott's disease) | 2HRZE / 10HRE | 12 months | CP extended; monthly follow-up with X-ray/MRI |
| Osteoarticular TB | 2HRZE / 10HRE | 12 months | Same as skeletal |
| Disseminated/Miliary TB | 2HRZE / 4HRE | 6 months (may extend) | Physician discretion for slow responders |
| Genitourinary TB | 2HRZE / 4HRE | 6 months | Standard |
Key Rule: CP needs to be extended to 24 weeks (6 months) for CNS TB and Skeletal TB. In disseminated TB or slow response, the treating physician may extend on a case-by-case basis.
4. SECOND-LINE ATT DRUGS (for Drug-Resistant TB)
WHO/NTEP Drug Group Classification (2022 Revised)
Group A (Prioritized - use all if possible):
- Levofloxacin (Lfx) or Moxifloxacin (Mfx) - fluoroquinolones
- Bedaquiline (Bdq) - inhibits mycobacterial ATP synthase
- Linezolid (Lzd/Lz) - oxazolidinone
Group B (Add next):
- Clofazimine (Cfz)
- Cycloserine (Cs) or Terizidone (Trd)
Group C (Use when Groups A & B insufficient):
- Ethambutol (E)
- Delamanid (Dlm) - nitroimidazole
- Pyrazinamide (Z)
- Imipenem-cilastatin or Meropenem
- Amikacin (Am) / Streptomycin (S)
- Ethionamide (Eto) / Prothionamide (Pto)
- p-aminosalicylic acid (PAS)
- Pretomanid (Pa) - used only as part of BPaL/BPaLM regimen
5. DRUG-RESISTANT TB REGIMENS (NTEP 2024)
A. Isoniazid Mono/Poly Resistance (H-resistant, R-sensitive)
Regimen: (6 or 9) Lfx R Z E
- No separate IP/CP
- Duration: 6 months (extend to 9 months for extensive disease, uncontrolled comorbidity, extrapulmonary TB, or positive smear at month 4)
B. MDR-TB / RR-TB (Rifampicin Resistant)
1. BPaLM Regimen (Priority - NTEP 2024 rollout):
| Drug | Dose |
|---|---|
| Bedaquiline (Bdq) | 400 mg/day × 2 weeks, then 200 mg 3×/week |
| Pretomanid (Pa) | 200 mg/day |
| Linezolid (Lzd) | 600 mg/day (may reduce to 300 mg) |
| Moxifloxacin (Mfx) | 400 mg/day (drop if FQ resistance documented) |
Duration: 6 months (all-oral)
- Cure rates >85%, replacing the old 18-24 month injectable-containing regimens
- Treatment extension if culture conversion fails at month 4-6 or treatment interruption >7 days
2. WHO Short-Course Oral Regimen (9-11 months):
- IP (4-6 months): Bdq + Lfx/Mfx + Eto + E + Z + high-dose H (Hh) + Cfz
- CP (5 months): Lfx/Mfx + Cfz + Z + E
- Can use Lzd replacing Eto (NTEG August 2024 recommendation)
C. XDR-TB / Treatment-Intolerant MDR-TB
BPaL Regimen (6 months):
- Bedaquiline + Pretomanid + Linezolid
- FDA-approved (2019), favorable outcomes in 89% in Nix-TB study
- Used when FQ resistance present (BPaLM drops moxifloxacin)
6. PEDIATRIC ATT (NTEP)
Standard regimen: 2HRZE / 4HRE (same structure as adults, weight-based dosing)
Pediatric Dispersible FDCs:
- IP: RHZ 75/50/150 mg (dispersible) + E 100 mg loose
- CP: RH 75/50 mg (dispersible) + E 100 mg loose
6 Pediatric Weight Bands (up to 39 kg):
| Weight | IP HRZ tabs | IP E tabs | CP HR tabs | CP E tabs |
|---|---|---|---|---|
| 4-7 kg | 1 | 1 | 1 | 1 |
| 8-11 kg | 2 | 2 | 2 | 2 |
| 12-15 kg | 3 | 3 | 3 | 3 |
| 16-24 kg | 4 | 4 | 4 | 4 |
| 25-29 kg | 3+1A | 3 | 3+1A | 3 |
| 30-39 kg | 2+2A | 2 | 2+2A | 2 |
(A = Adult FDC added for children >25 kg who can swallow tablets)
Pediatric TB Meningitis: 2HRZE + 10HRE; Prednisolone 2 mg/kg/day × 4 weeks, then taper
Pediatric Osteoarticular/Spine TB: 2HRZE + 10HRE (12 months total)
7. INDICATIONS FOR ATT
Confirmed TB (start treatment)
- Bacteriologically confirmed: Sputum smear positive, CBNAAT/Xpert positive, culture positive
- Clinically diagnosed pulmonary TB: Radiological evidence + symptoms (cough >2 weeks, fever, weight loss, night sweats) + response to ATT
- All forms of extrapulmonary TB (lymph node, pleural, pericardial, CNS, skeletal, GU, abdominal)
- Disseminated/Miliary TB
Special Populations Requiring ATT
- HIV-TB coinfection: Start ATT first, then ART (2-8 weeks later); use rifampicin-based regimen; avoid stavudine-based ART
- Pediatric TB (<18 years): Same 2HRZE/4HRE but dispersible weight-based FDCs
- Pregnant women: 2HRZE/4HRE is safe; streptomycin is contraindicated (ototoxicity to fetus); pyridoxine supplementation essential
- Latent TB Infection (LTBI): TPT (TB Preventive Therapy) - 6H, 3HP (isoniazid + rifapentine weekly × 12 doses) or 4R (rifampin × 4 months)
8. CONTRAINDICATIONS & PRECAUTIONS
Absolute Contraindications
| Drug | Absolute Contraindication |
|---|---|
| Streptomycin | Pregnancy (Category X - fetal ototoxicity/deafness) |
| Pyrazinamide | Severe hepatic insufficiency (Child-Pugh C), acute liver failure |
| Ethambutol | Pre-existing optic neuritis; inability to monitor visual acuity |
| Isoniazid | Severe drug-induced hepatitis (ALT >5× ULN with symptoms) |
| Rifampicin | Severe hypersensitivity reaction; concurrent use with certain ARVs (lopinavir/ritonavir without dose adjustment) |
| Bedaquiline | Severe hepatic impairment; concurrent strong CYP3A4 inducers (rifampicin - avoid combination); QTc >500 ms |
| Pretomanid | Severe hepatic impairment |
| Linezolid | Concurrent serotonergic agents (serotonin syndrome risk); severe thrombocytopenia |
| Fluoroquinolones | Children <18 years (relative - cartilage toxicity); pregnancy (relative) |
Relative Contraindications / Precautions
| Situation | Drug to Avoid / Modify |
|---|---|
| Renal failure (GFR <30) | Reduce/avoid ethambutol, aminoglycosides, cycloserine |
| Hepatic disease | Avoid/reduce PZA; use 2HRE or 9HR if PZA must be omitted |
| Epilepsy/psychosis history | Caution with cycloserine (seizures, psychosis risk) |
| Active alcohol abuse | Cycloserine contraindicated under DOT only |
| Hyperuricemia/gout | Pyrazinamide (raises uric acid) - use cautiously |
| Age >75 years | Some experts omit PZA in modest disease (though recent evidence doesn't confirm higher PZA toxicity in elderly) |
| Visual impairment (baseline) | Monitor ethambutol closely; consider dose reduction |
9. WHEN TO MODIFY ATT
A. Adverse Drug Reactions (ADRs) Requiring Modification
| ADR | Likely Drug | Action |
|---|---|---|
| Hepatotoxicity (ALT >3× ULN + symptoms, or >5× ULN asymptomatic) | H, R, Z (in that order of likelihood) | Stop all ATT; restart in sequential challenges once ALT <2× ULN; use 2SE/6 months alternative if severe |
| Peripheral neuropathy | Isoniazid | Add Pyridoxine 25-50 mg/day; if severe, replace H |
| Optic neuritis (color vision loss, decreased acuity) | Ethambutol | Stop E immediately; replace with streptomycin or fluoroquinolone |
| Ototoxicity / vestibulotoxicity | Streptomycin, Amikacin | Stop aminoglycoside; substitute |
| Orange discoloration (skin, urine, tears) | Rifampicin | Normal effect - no change required; counsel patient |
| QT prolongation (>500 ms on ECG) | Bedaquiline, Moxifloxacin, Clofazimine | Hold offending drug; ECG monitoring; electrolyte correction |
| Thrombocytopenia / hemolytic anemia | Rifampicin | Stop R; use alternate regimen |
| Cutaneous reactions (rash, urticaria) | Any drug | Mild: antihistamines; Severe (Stevens-Johnson): stop all ATT, rechallenge one by one |
| Psychosis / seizures | Cycloserine, Isoniazid | Reduce dose or stop; add pyridoxine for INH-related issues |
| Peripheral neuropathy (severe) | Linezolid | Reduce dose to 300 mg/day or dose-pause |
| Arthralgias/Hyperuricemia | Pyrazinamide | Allopurinol; if severe, stop Z (extend treatment duration) |
B. Clinical Situations Requiring Modification/Extension
| Situation | Modification |
|---|---|
| Culture positive at 2 months | Continue IP (IP may be extended by 4 weeks); review drug susceptibility |
| Smear/culture positive at end of treatment | Declare treatment failure; refer for DST and DR-TB management |
| CNS TB (meningitis) | Extend CP to 10 months (total 12 months); add steroids |
| Skeletal/Spinal TB | Extend CP to 10 months (total 12 months) |
| Omission of PZA (due to ADR) | Extend total treatment to at least 9 months |
| HIV coinfection with CD4 <100 | Consider extending to 9 months; avoid rifabutin interactions |
| Hepatic disease (can't use PZA or H) | Alternative: 2 months SRE + 10 months RE (12 months) or 9HRE |
| Pregnancy | Use 2HRZE/4HRE; avoid streptomycin; give pyridoxine 10 mg/day |
| Diabetes | Higher doses may be needed; rifampicin reduces oral hypoglycemics (monitor HbA1c) |
| Renal failure | Adjust E and aminoglycoside doses; rifampicin and isoniazid are safe |
| Treatment interruption | If IP interrupted: restart if >2 weeks missed; if CP interrupted >2 months, restart from beginning |
10. TB PREVENTIVE THERAPY (TPT) - NTEP 2025 Updates
| Regimen | Population | Duration |
|---|---|---|
| 3HP (Isoniazid 900 mg + Rifapentine 900 mg weekly, DOT) | All household contacts, PLHIV, age >2 years | 3 months |
| 6H (Isoniazid 5 mg/kg/day) | Child contacts <5 years; PLHIV | 6 months |
| 4R (Rifampin daily) | HIV-negative; children | 4 months |
| 3HR (Isoniazid + Rifampin daily) | HIV-negative adults/children | 3 months |
TPT is not recommended in active TB disease, history of adequate TB treatment, or allergy to isoniazid/rifamycins.
11. PYRIDOXINE (Vitamin B6) SUPPLEMENTATION
Pyridoxine 10 mg/day (children) or 25-50 mg/day (adults) is given with isoniazid in:
- Pregnant women
- Malnourished patients
- Alcoholics
- Diabetics
- HIV-positive patients
- Elderly patients
- Those with peripheral neuropathy risk
12. KEY 2025 PEER-REVIEWED GUIDELINE UPDATES
-
ATS/CDC/ERS/IDSA 2025 Guideline (PMID 40693952) - recommends the new 4-month regimen (2HPMZ/2HPM) for eligible pulmonary DS-TB patients and BPaLM/BPaL for DR-TB.
-
NTEP November 2024 DR-TB Guidelines (tbcindia.mohfw.gov.in) - officially introduced BPaLM under programmatic conditions, CBNAAT M.tb/XDR testing, and Lzd replacing Eto in shorter oral MDR-TB regimen.
-
WHO 2022 Recommendations - reclassified XDR-TB (now includes MDR-TB + any FQ resistance + at least one Group A drug resistance); endorsed BPaLM as priority regimen.
13. MONITORING DURING ATT
| Parameter | Frequency | Drug Monitored For |
|---|---|---|
| Liver function tests (ALT/AST) | Baseline; monthly if risk factors | H, R, Z hepatotoxicity |
| Visual acuity + color vision | Monthly | Ethambutol optic neuritis |
| Serum uric acid | Baseline; monthly | Pyrazinamide |
| ECG (QTc) | Baseline; weeks 2, 4, 8, 12 | Bedaquiline, Mfx, Cfz |
| Sputum smear/culture | End of IP (month 2); month 5; end of treatment | Treatment response |
| CBC, renal function | For aminoglycosides/linezolid | Nephrotoxicity, myelosuppression |
| Audiology | For aminoglycosides | Ototoxicity |
Sources: Harrison's Principles of Internal Medicine 22E (2025) | Murray & Nadel's Textbook of Respiratory Medicine | Tintinalli's Emergency Medicine | ICMR/NTEP Drug-Sensitive TB Treatment Guidelines (2022) | NTEP National Guidelines for DR-TB Management (November 2024) | ATS/CDC/ERS/IDSA Clinical Practice Guideline 2025 (PMID 40693952) | WHO TB Knowledge Sharing Platform
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